A major part of the proposed work is a detailed investigation of the effects of fluoride ions on peptidoglycan synthesis in bacteria, with particular attention to bacteria found in dental plaque. Fluoride has been found to be a bacteriolytic agent when present in growth media. The responses of plaque bacteria to fluoride are in many respects similar to their responses to penicillin. Bacteria with highly active autolytic systems undergo lysis following growth in the presence of penicillin or fluoride. Bacteria without such active autolytic systems do not undergo lysis but do form defective cell walls. The action of fluoride appears to involve synthesis of abnormal peptidoglycan that is unusually sensitive to autolytic enzymes. We want to determine the specific biochemical reactions in peptidoglycan synthesis that are affected by fluoride and the nature of the abnormal product of synthesis. Other parts of the project include development and exploitation of pellet culture systems for growing plaque bacteria in crowded conditions, further studies of ion-exchange reactions of plaque bacteria and work with plaque bacteria rendered hypersensitive to host defense mechanisms following growth in fluoride-containing media.